Many investigators consider thrombosis to be the initiating event in acute atherosclerotic catastrophes such as stroke and myocardial infarction, which occur with great frequency in patients with high blood concentrations of beta or prebeta lipoproteins. Our goals are to define more exactly the interrelationships among plasma lipoprotein concentrations, blood platelet composition and function, and intravascular coagulation, especially as they relate to the initiation of thrombus formation in atherosclerosis and its sequelae. Platelet function will be evaluated, in patients with hyperlipidemia and atherosclerosis, by means of studies of platelet aggregation and 14C-serotonin release. Hypersensitivity to aggregating agents and increased serotonin release will be correlated with altered platelet composition and alterations in platelet prostaglandin-endoperoxide production. The presence of hyperlipidemia and of atherosclerosis will be correlated, as well, with evidence of intravascular coagulation (determined by gel filtration of plasma), and with abnormalities in fibrinolysis (determined directly by the euglobulin lysis method, as well as by plasma fibrin-split-product determination). The effects of antithrombotic and lipid-lowering drugs on these systems will be tested. Lastly, the cholesterol-fed rabbit will be used as an animal model for the effects of hypercholesterolemia on hemostatic mechanisms.